CA2446157A1 - Methods for screening substances in a microwell array - Google Patents
Methods for screening substances in a microwell array Download PDFInfo
- Publication number
- CA2446157A1 CA2446157A1 CA 2446157 CA2446157A CA2446157A1 CA 2446157 A1 CA2446157 A1 CA 2446157A1 CA 2446157 CA2446157 CA 2446157 CA 2446157 A CA2446157 A CA 2446157A CA 2446157 A1 CA2446157 A1 CA 2446157A1
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- liquid
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- G01N35/00069—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
Methods for manufacturing and using an apparatus for manipulating and analyzing a large number of microscopic samples of a liquid or materials, including cells, in liquid suspension. Parallel through-holes (12) are formed in a platen (10) and loaded with a liquid. Loading may be performed in such a way as to create a gradient, with respect to the position of the through-holes, of the concentration of a particular substance or of another quantity.
Mixing of the contents of through-holes may be obtained by bringing filled microwell arrays into contact with each other with registration of individuals through-holes.
Mixing of the contents of through-holes may be obtained by bringing filled microwell arrays into contact with each other with registration of individuals through-holes.
Claims (26)
1. A method for loading a plurality of disparate sample containers, the sample containers comprising an integral structure, such that the concentration of a specified substance in each container is characterized by a gradient with respect to position of the container within the structure, the method comprising:
a. introducing a first liquid into the disparate containers; and b. contacting the containers with a second liquid, the second liquid containing the specified substance, in such a manner that the degree of diffusion of the specified substance into the disparate containers differs in a controlled manner among the containers.
a. introducing a first liquid into the disparate containers; and b. contacting the containers with a second liquid, the second liquid containing the specified substance, in such a manner that the degree of diffusion of the specified substance into the disparate containers differs in a controlled manner among the containers.
2. A method according to claim 1, wherein contacting the containers with the second liquid includes differing a duration of contact with the second liquid as among the disparate containers.
3. A method according to claim 1, wherein contacting the containers with the second liquid includes modulating the diffusion rate of the specified substance into the containers.
4. A method according to claim 3, further comprising the step of creating a gradient of the specified substance in the second liquid prior to contacting the containers with the second liquid.
5. A method according to claim 4, wherein the step of creating a gradient of the specified substance includes applying electrophoresis.
6. A method according to claim 3, wherein the step of modulating the diffusion rate includes contacting the containers with the second liquid through a membrane having a permeability variable with respect to position.
7. A method according to claim 1, wherein the step of introducing a first liquid into the disparate containers includes filling a platen having a plurality of through-holes.
8. A method for loading a liquid into a plurality of through-holes of a platen, the platen having a top surface, the top surface having an opening to each through-hole, the method comprising:
a. forming a droplet of the liquid on the end of a liquid transfer device;
b. moving the fluid transfer device so as to drag the droplet across the top surface of the platen and over the through-holes to be filled;
c. dispensing the liquid in such a manner as to keep the droplet from being depleted;
and d. withdrawing the droplet from the surface after the through-holes are filled.
a. forming a droplet of the liquid on the end of a liquid transfer device;
b. moving the fluid transfer device so as to drag the droplet across the top surface of the platen and over the through-holes to be filled;
c. dispensing the liquid in such a manner as to keep the droplet from being depleted;
and d. withdrawing the droplet from the surface after the through-holes are filled.
9. A method for loading a liquid sample into a plurality of through-holes of a platen, the method comprising:
a. filling a plurality of capillary tubes having dispensing ends, the capillary tubes comprising an array;
b. disposing each dispensing end in proximity to a distinct through-hole; and c. transferring liquids to the through-holes of the platen through the capillary tubes.
a. filling a plurality of capillary tubes having dispensing ends, the capillary tubes comprising an array;
b. disposing each dispensing end in proximity to a distinct through-hole; and c. transferring liquids to the through-holes of the platen through the capillary tubes.
10. A method for loading a plurality of sample containers, the sample containers comprising an integral structure, such that the concentration of a specified substance in each container is characterized by a gradient with respect to position of the container within the structure, the method comprising:
a. creating regions of distinct concentration of the specified substance in a liquid, the liquid having a surface; and b. transferring into distinct containers the liquid from the distinct regions.
a. creating regions of distinct concentration of the specified substance in a liquid, the liquid having a surface; and b. transferring into distinct containers the liquid from the distinct regions.
11. A method according to claim 10, wherein the step of creating regions of distinct concentration includes applying electrophoresis.
12. A method according to claim 10, wherein the step of transferring liquid includes transporting the liquid through capillary tubes.
13. A method according to claim 10, wherein the step of transferring the liquid includes contacting the integral structure with the surface of the liquid.
14. A method for manufacturing a platen having two substantially parallel planar surfaces and a plurality of through-holes disposed substantially perpendicularly to the planar surfaces, the method comprising:
a. providing a sheet of thermoplastic material;
b. loading the sheet of thermoplastic material into contact with a surface of a die having a plurality of holes; and c. bringing a punch having a plurality of protrusions of specified cross-section into contact with the sheet of thermoplastic material in such a manner that the protrusions are in alignment with the holes of the die such that through-holes are cut through the thermoplastic material.
a. providing a sheet of thermoplastic material;
b. loading the sheet of thermoplastic material into contact with a surface of a die having a plurality of holes; and c. bringing a punch having a plurality of protrusions of specified cross-section into contact with the sheet of thermoplastic material in such a manner that the protrusions are in alignment with the holes of the die such that through-holes are cut through the thermoplastic material.
15. A method for manufacturing a platen having two substantially parallel planar surfaces and a plurality of through-holes disposed substantially perpendicularly to the planar surfaces, the method comprising:
a. providing a sheet of electrically conducting material;
b. loading the sheet of conducting material into contact with a surface of a die having a plurality of holes; and c. bringing an EDM mandrel having a plurality of protrusions of specified cross-section into proximity of the sheet of conducting material in such a manner that the protrusions are in alignment with the holes of the die such that through-holes are cut through the conducting material.
a. providing a sheet of electrically conducting material;
b. loading the sheet of conducting material into contact with a surface of a die having a plurality of holes; and c. bringing an EDM mandrel having a plurality of protrusions of specified cross-section into proximity of the sheet of conducting material in such a manner that the protrusions are in alignment with the holes of the die such that through-holes are cut through the conducting material.
16. A method for providing a hydrophobic coating to a silicon platen having a first and a second surface, the surfaces being substantially parallel, and a plurality of through-holes substantially perpendicular to the surfaces, the method comprising:
a. oxidizing the first surface;
b. cleaning the oxidized first surface;
c. applying a positive pressure of inert gas to the plurality of through-holes from the direction of the second surface; and d. exposing the first surface to a silanizing vapor agent.
a. oxidizing the first surface;
b. cleaning the oxidized first surface;
c. applying a positive pressure of inert gas to the plurality of through-holes from the direction of the second surface; and d. exposing the first surface to a silanizing vapor agent.
17. A method for loading a liquid into a plurality of through-hole platens, each platen having a plurality of through-holes, the method comprising:
a. stacking at least two platens together in such an adjacent manner that at least one of the plurality of through-holes from each platen is registered with a through-hole of each other adjacent platen so as to form at least one continuous channel;
and b. transferring the liquid into each continuous channel.
a. stacking at least two platens together in such an adjacent manner that at least one of the plurality of through-holes from each platen is registered with a through-hole of each other adjacent platen so as to form at least one continuous channel;
and b. transferring the liquid into each continuous channel.
18. A method according to claim 17, wherein each platen is separated from each adjacent platen by an air gap.
19. A method according to claim 17, wherein the step of transferring liquid includes transporting the liquid through capillary tubes.
20. A method according to claim 17, wherein the step of transferring liquid includes transporting the liquid through at least one cannula.
21. A method for mixing liquid in at least two platens, each platen having a plurality of through-holes, the method comprising stacking at least two platens together for a specified time, in such a manner that at least one of the plurality of through-holes from each platen connects with a corresponding through-hole of another platen such that liquid is allowed to diffuse between connecting through-holes.
22. A method according to claim 21, further including the step of separating the at least two platens after mixing of the liquid between the connecting through-holes.
23. A microlens array for diffusing light, the microlens array comprising, a. a microchannel plate having a plurality of parallel microchannels; and b. a liquid disposed within substantially each of the plurality of the parallel microchannel.
24. A method for humidifying a system, the method comprising, a. filling a microchannel plate with a liquid having a plurality of parallel microchannels; and b. placing the filled microchannel plate in vicinity of the system to be humidified.
25. A method for diffusing light, the method comprising:
a. entraining a fluid in substantially each of a plurality of parallel microchannels having proximal and distal ends, the microchannels comprising a microchannel plate;
b. illuminating the proximal end of each of the plurality of parallel microchannels with light; and c. allowing diffuse light to emanate from the distal ends of the microchannel.
a. entraining a fluid in substantially each of a plurality of parallel microchannels having proximal and distal ends, the microchannels comprising a microchannel plate;
b. illuminating the proximal end of each of the plurality of parallel microchannels with light; and c. allowing diffuse light to emanate from the distal ends of the microchannel.
26. A perforated platen having substantially parallel planar surfaces for manipulating distinct liquid samples, each sample having a volume less than 1 microliter, the platen comprising:
a. an inner layer of hydrophilic material;
b. two outer layers of hydrophobic material coupled to opposite sides of the inner layer; and c. a two-dimensional array of through-holes, at least two holes having distinct volumes, for retaining the distinct liquid samples, the through-holes each having a diameter less than 300 micrometers and traversing the inner layer and the two outer layers in a direction substantially perpendicular to the planar surfaces of the platen.
a. an inner layer of hydrophilic material;
b. two outer layers of hydrophobic material coupled to opposite sides of the inner layer; and c. a two-dimensional array of through-holes, at least two holes having distinct volumes, for retaining the distinct liquid samples, the through-holes each having a diameter less than 300 micrometers and traversing the inner layer and the two outer layers in a direction substantially perpendicular to the planar surfaces of the platen.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CA 2665706 CA2665706A1 (en) | 2001-05-07 | 2002-05-07 | Methods for screening substances in a microwell array |
Applications Claiming Priority (3)
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US09/850,123 US6893877B2 (en) | 1998-01-12 | 2001-05-07 | Methods for screening substances in a microwell array |
US09/850,123 | 2001-05-07 | ||
PCT/US2002/014357 WO2002089982A2 (en) | 2001-05-07 | 2002-05-07 | Methods for screening substances in a microwell array |
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CA 2665706 Division CA2665706A1 (en) | 2001-05-07 | 2002-05-07 | Methods for screening substances in a microwell array |
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CA2446157A1 true CA2446157A1 (en) | 2002-11-14 |
CA2446157C CA2446157C (en) | 2010-11-16 |
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CA 2446157 Expired - Lifetime CA2446157C (en) | 2001-05-07 | 2002-05-07 | Methods for screening substances in a microwell array |
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- 2002-05-07 JP JP2002587105A patent/JP4741042B2/en not_active Expired - Lifetime
- 2002-05-07 CA CA 2665706 patent/CA2665706A1/en not_active Abandoned
- 2002-05-07 WO PCT/US2002/014357 patent/WO2002089982A2/en active Application Filing
- 2002-05-07 CA CA 2446157 patent/CA2446157C/en not_active Expired - Lifetime
- 2002-05-07 EP EP20020769364 patent/EP1385628A2/en not_active Withdrawn
-
2004
- 2004-04-08 US US10/820,679 patent/US20040191924A1/en not_active Abandoned
- 2004-10-05 US US10/958,969 patent/US7547556B2/en not_active Expired - Lifetime
-
2008
- 2008-04-11 JP JP2008103292A patent/JP4607202B2/en not_active Expired - Lifetime
- 2008-05-12 JP JP2008124416A patent/JP2008292478A/en active Pending
- 2008-09-17 JP JP2008237574A patent/JP2009096992A/en active Pending
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2009
- 2009-05-19 US US12/468,417 patent/US8029745B2/en not_active Expired - Fee Related
-
2011
- 2011-01-12 JP JP2011003611A patent/JP5103536B2/en not_active Expired - Lifetime
- 2011-09-09 US US13/229,208 patent/US20110319300A1/en not_active Abandoned
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EP1385628A2 (en) | 2004-02-04 |
JP2005507492A (en) | 2005-03-17 |
US20040191924A1 (en) | 2004-09-30 |
US20110319300A1 (en) | 2011-12-29 |
JP4741042B2 (en) | 2011-08-03 |
WO2002089982A3 (en) | 2003-01-23 |
JP2008268202A (en) | 2008-11-06 |
US8029745B2 (en) | 2011-10-04 |
CA2446157C (en) | 2010-11-16 |
JP2009096992A (en) | 2009-05-07 |
JP2011095271A (en) | 2011-05-12 |
US20020001546A1 (en) | 2002-01-03 |
JP4607202B2 (en) | 2011-01-05 |
US20090258797A1 (en) | 2009-10-15 |
JP5103536B2 (en) | 2012-12-19 |
US20050079105A1 (en) | 2005-04-14 |
CA2665706A1 (en) | 2002-11-14 |
WO2002089982A2 (en) | 2002-11-14 |
JP2008292478A (en) | 2008-12-04 |
US6893877B2 (en) | 2005-05-17 |
US7547556B2 (en) | 2009-06-16 |
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